p53 protein is a 53 kd nuclear phosphoprotein, encoded by the p53 gene, a tumor suppressor gene acting probably as a negative regulator of cell growth. The single copy of the human p53 gene is on chromosome 17p and loss of homozygosity in this locus is frequently found in common human cancers such as breast, colon, small lung cell carcinoma and astrocytoma. In addition, recent findings strongly suggest that point mutations and altered expression of p53 is the most frequent known genetic change in human cancer. In collaboration with Dr. C. Felix et al., we have recently shown the existence of p53 mutations in a significant proportion of cases of childhood rhabdomyosarcoma. There is evidence to support that the mechanism by which mutant p53 gene affects tumor growth is through its mutant p53 proteins whose half-lives are markedly increased as a result of formed complexes with the heat shock proteins. In this way, the levels of these mutant p53 proteins are comparable to those known to exert a "trans- dominant loss of function" effect on wild type p53 protein, which is found decreased in tumors expressing p53 gene mutations. Immunohistochemical studies of breast and colon carcinomas using antibodies against p53 protein have shown association of these proteins with high grade tumors and a potential prognostic role of this protein in human malignancy. Antibodies specific to wild or mutant p53 proteins have now become commercially available. We will use these antibodies to stain paraffin-embedded rhabdomyosarcomas of the alveolar and embryonal histologic subtypes before and after disease progression, and will compare p53 expression with histologic subtype, clinical stage and outcome. This study will help us answer the question if there is a potential role of the p53 gene in the development and prognosis of childhood rhabdomyosarcoma.